Growth Rate Analysis and Efficient Experimental Design for Tumor Xenograft Studies

Hather, Gregory; Liu, Ray; Bandi, Syamala; Mettetal, Jerome; Manfredi, Mark; Shyu, Wen-Chyi; Donelan, Jill; Chakravarty, Arijit

doi:10.4137/cin.s13974

Cited by 97 publications

(126 citation statements)

References 20 publications

(29 reference statements)

Supporting

Mentioning

121

Contrasting

Order By: Relevance

“…Tumor growth rate was determined as previously described (38). Briefly, tumor volumes were calculated using the modified formula for an ellipsoid: 1 / 2 (length × width 2 ).…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner

et al. 2017

View full text Add to dashboard Cite

Using a novel mouse model, a mitochondrial-nuclear exchange model termed MNX, we tested the hypothesis that inherited mitochondrial haplotypes alter primary tumor latency and metastatic efficiency. Male FVB/N-Tg(MMTVneu)202Mul/J (Her2) transgenic mice were bred to female MNX mice having FVB/NJ nuclear DNA with either FVB/NJ, C57BL/6J, or BALB/cJ mtDNA. Pups receiving the C57BL/6J or BALB/cJ mitochondrial genome (i.e., females crossed with Her2 males) showed significantly (P < 0.001) longer tumor latency (262 vs. 293 vs. 225 days), fewer pulmonary metastases (5 vs. 7 vs. 15), and differences in size of lung metastases (1.2 vs. 1.4 vs. 1.0 mm diameter) compared with FVB/NJ mtDNA. Although polyoma virus middle T–driven tumors showed altered primary and metastatic profiles in previous studies, depending upon nuclear and mtDNA haplotype, the magnitude and direction of changes were not the same in the HER2-driven mammary carcinomas. Collectively, these results establish mitochondrial polymorphisms as quantitative trait loci in mammary carcinogenesis, and they implicate distinct interactions between tumor drivers and mitochondria as critical modifiers of tumorigenicity and metastasis.

show abstract

“…Tumor growth rate was determined as previously described (38). Briefly, tumor volumes were calculated using the modified formula for an ellipsoid: 1 / 2 (length × width 2 ).…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner

et al. 2017

View full text Add to dashboard Cite

show abstract

“…c ). Furthermore, the mean tumor growth rate over the entire experiment (70 days) was significantly slower in M30‐treated mice ( p = 0.0337, effect size: Cohen's d = 1.02) (Fig. d ).…”

Section: Resultsmentioning

confidence: 93%

“…Tumors were measured with a digital caliper and volume was calculated as (L × W 2 )/2. The mean tumor growth rate was derived from the slope of log10 transformed tumor volumes and was calculated as previously described . Briefly, small tumor volumes were truncated at 50 mm 3 since very low values can become extreme when using log transformations.…”

Section: Methodsmentioning

confidence: 99%

“…The mean tumor growth rate was derived from the slope of log10 transformed tumor volumes and was calculated as previously described. 37 Briefly, small tumor volumes were truncated at 50 mm 3 since very low values can become extreme when using log transformations. Then, volumes were log10 transformed, a linear regression line was fit to each mouse, and the slope was calculated.…”

Section: In Vivo Adoptive Cell Transfermentioning

confidence: 99%

See 1 more Smart Citation

Optimizing T‐cell receptor avidity with somatic hypermutation

Bassan

Gozlan

Sharbi‐Yunger

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Adoptive transfer of T cells that have been genetically modified to express an antitumor T‐cell receptor (TCR) is a potent immunotherapy, but only if TCR avidity is sufficiently high. Endogenous TCRs specific to shared (self) tumor‐associated antigens (TAAs) have low affinity due to central tolerance. Therefore, for effective therapy, anti‐TAA TCRs with higher and optimal avidity must be generated. Here, we describe a new in vitro system for directed evolution of TCR avidity using somatic hypermutation (SHM), a mechanism used in nature by B cells for antibody optimization. We identified 44 point mutations to the Pmel‐1 TCR, specific for the H‐2Db‐gp10025‐33 melanoma antigen. Primary T cells transduced with TCRs containing two or three of these mutations had enhanced activity in vitro. Furthermore, the triple‐mutant TCR improved in vivo therapy of tumor‐bearing mice, which exhibited improved survival, smaller tumors and delayed or no relapse. TCR avidity maturation by SHM may be an effective strategy to improve cancer immunotherapy.

show abstract

“…Both HCQ and CMQ significantly slowed tumor growth compared to vehicle, with CMQ exhibiting slight improvement over HCQ ( Figure 5B). Tumor growth inhibition was evaluated by a growth rate analysis approach 34 . HCQ significantly decreased the rate of tumor growth compared to vehicle, but CMQ showed a greater magnitude of tumor growth inhibition compared to both vehicle and HCQ ( Figure 5C).…”

Section: Cmq Displays Single Agent Anti-tumor Activity In a Mouse Mmentioning

confidence: 99%

Novel organometallic chloroquine derivative inhibits tumor growth

Hall

Ramsey

Peng

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Autophagy has emerged as a mechanism critical to both tumorigenesis and development of resistance to multiple lines of anti-cancer therapy. Therefore, targeting autophagy and alternative cell death pathways has arisen as a viable strategy for refractory tumors. The anti-malarial 4-aminoquinoline compounds chloroquine and hydroxychloroquine are currently being considered for re-purposing as anti-cancer therapies intended to sensitize different tumors by targeting the lysosomal cell death pathway. Here, we describe a novel organometallic chloroquine derivative, cymanquine, that exhibits enhanced bioactivity compared to chloroquine in both normal, and reduced pH tumor microenvironments, thus overcoming a defined limitation of traditional 4-aminoquinolines. In vitro, cymanquine exhibits greater potency than CQ in a diverse panel of human cancer cell lines, including melanoma, in both normal pH and in reduced pH conditions that mimic the tumor microenvironment. Cymanquine treatment results in greater lysosomal accumulation than chloroquine and induces lysosomal dysfunction leading to autophagy blockade. Using a mouse model of vemurafenib-resistant melanoma, cymanquine slowed tumor growth greater than hydroxychloroquine, and when used in combination with vemurafenib, cymanquine partially restored sensitivity to vemurafenib. Overall, we show that cymanquine exhibits superior lysosomal accumulation and autophagy blockade than either chloroquine or hydroxychloroquine in vitro; and in addition to its high level of tolerability in mice, exhibits superior in vivo efficacy in a model of human melanoma.

show abstract

Growth Rate Analysis and Efficient Experimental Design for Tumor Xenograft Studies

Cited by 97 publications

References 20 publications

Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner

Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner

Optimizing T‐cell receptor avidity with somatic hypermutation

Novel organometallic chloroquine derivative inhibits tumor growth

Contact Info

Product

Resources

About